Isolation of holostane-type saponins from the black sea cucumber Holothuria atra and evaluating their anti-allergic activity: in vitro and in silico study

Abstract

Sea cucumbers are both versatile marine organisms and an Asian marine food known to have several medicinal effects. We evaluated the anti-allergic potential of some major purified holostane-type saponins from the body wall of the black sea cucumber, Holothuria atra. Six saponin compounds were isolated, holothurin B (1), holothurin A (2), 24-dehydro echinoside A (3), desholothurin A1 (4), desholothurin A (5), and des 24-dehydro echinoside A (6). The structures were identified based on spectroscopic methods and by comparison with the literature. Each compound’s inhibitory activity toward the release of β-hexosaminidase was evaluated. Among the six compounds, holothurin B (1) showed the strongest inhibition of the degranulation at all tested concentrations in a dose-dependent manner, compared to the positive control, quercetin. We also observed that holothurin B (1) was able to alleviate the inflammatory mediators interleukin (IL)-6, IL-13, and tumor necrosis factor-alpha (TNF-α). Holothurin B (1) also inhibited the Ca²⁺ influx stimulated by the calcium ionophore A23187, by suppressing the expression of inositol-1,4,5-triphosphate receptor (IP3R) mRNA. These results suggest that (i) holothurin B (1) has good anti-allergy activity without cytotoxicity at effective concentrations, and (ii) this compound could be a lead compound for the treatment of allergic diseases and associated inflammation. We also performed a molecular docking study for the tested compounds to correlate their binding modes and affinity for the IP3R with the in vitro results. The results concluded that the holostane-type saponins could be used as anti-allergy agents, which may be attributed to their holostane group.